数字化病理切片构建功能影像验证平台及其在非小细胞肺癌生物靶区中的应用

The development of functional image and intensity modulated radiotherapy promote the new concept of biologically conformal radiation therapy,which is a direction for radiotherapy development.Fusion of functional and anatomical image PET/CT provides a noninvasive method to detctive biological characteristics of tumor.On the base of the previous research results of validation for target volume contouring on PET/CT with pathological sections,this research use the digital pathological section technology, to put whole tumor specimen into digital pathological image match to PET/CT image,and analyse the immunohistochemical staining on pathological sections with image analysis software, which provide abundant molecular biology information. By this way,we build up a pathological validation methods to provide qualitative, quantitative and positioning information for PET/CT image.Using this pathological validation method to validate the efficiency and accuracy of three isotope contrast agents (FMISO,FLT and FDG) for NSCLC with PET/CT scan, and find the appropriate method to contour biological target volume.By means of the external irradiation on animal transplant tumor model, we want to investigate the role of these isotope contrast agents on therapeutic monitoring of radiotherapy.The purpose this study is to provide the scientific proof for biologically conformal radiation therapy and therapeutic monitoring of radiotherapy.

功能影像和调强放射治疗技术的发展促进了生物学适形调强放疗概念的产生，并成为放射肿瘤学发展的方向。功能解剖融合影像PET/CT是无创性检测肿瘤生物学特性的重要手段。本研究在前期应用病理大切片验证PET/CT靶区勾画的工作基础上，利用数字化病理切片技术，将肿瘤整体标本制成与PET/CT影像精确对应的数字化病理影像，通过对病理切片的免疫组化染色，并利用病理图像分析软件分析，为对应的PET/CT影像提供丰富的分子生物学信息，从而建立一套为PET/CT影像提供定位、定量和定性的病理学验证方法。并利用此方法验证乏氧显像剂FMISO、增殖显像剂FLT和传统的代谢显像剂FDG对非小细胞肺癌不同生物靶区勾画的有效性和准确性，明确最佳的生物靶区勾画方法。并通过动物移植瘤模型体外照射实验研究上述显像剂在放疗疗效监测中的作用。通过上述研究，为进一步实现生物学适形放疗和疗效监测提供科学依据。

目的　探讨非小细胞肺癌（NSCLC）18F-FDG, 18F-FLT, 18F-FMISO PET显像所示高摄取区与肿瘤细胞高增殖区的一致性。 .方法 选择14例初治、接受根治性手术切除治疗的NSCLC患者。 术前3天分别行18F-FDG, 18F-FLT, 18F-FMISO PET/CT显像，FDG以SUV2.5阈值勾画高摄取区，FLT以最大标准摄取值（SUVmax）的80%为阈值勾画高摄取区。术后肺肿瘤按体内方向还原，4mm层厚制作肺癌病理大切片并行HE 染色及Glut-1、Ki-67、HIF-1染色，免疫组化指数 ＞20%的区域为高表达区，PET图像与病理图像进行配准后比较高摄取区与高表达区是否匹配。. 结果　2例FMISO PET显像不佳。6例FDG PET高摄取区域与Glut-1高表达区不一致；2例FLT PET高摄取区与Ki-67高表达区一致。 .结论 　NSCLC肿瘤18F-FLT PET显像高摄取区与Ki-67高表达部分病人一致，说明生物靶区有可能实现，但是仍需要谨慎。